Labelling and generics: who is accountable?

Published: 30-Jun-2016

Bindu Narang, Director of Regulatory Affairs and Scientific Writing, Sciformix Corporation, considers the impact of proposed US FDA labelling regulations on the generic drugs sector

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On 12 April 2016, a group of 15 healthcare stakeholders wrote to the US Food and Drug Administration (FDA) expressing concerns that the FDA Proposed Rule to change generic drug label requirements could create provider and prescriber confusion and add significant avoidable costs to an already strained healthcare system.1

Nearly 8 in 10 prescriptions filled in the US are for generic drugs. The use of generics is expected to grow during the next few years as a number of popular drugs come off patent.2 Under regulations by the FDA, generic drugs must be chemically equivalent, have the same active ingredients and be bioequivalent to their branded counterparts.

However, the onus for safety monitoring appears to rest on the innovator, whose label is the Reference Listed Drug (RLD). Most notably, while a branded drug manufacturer is responsible for the accuracy and adequacy of its drug label, a generic drug company is responsible for ensuring that its label is the same as the label of the brand-name RLD.

Of several labelling regulations expected this year, the one with the greatest impact would be the proposed rule regarding labelling of generic drugs by the US FDA. The proposed rule asks generic drug companies to update their labels with new safety information as their reference product counterparts have done for almost 30 years. The FDA announced recently that this much-debated rule would be released in late 2016, but the different generic stakeholders are protesting against it.

Existing labelling process complexities

Product labelling is a collaborative process, from initiation of a clinical trial to commercialisation, with multiple sources of inputs that result in a company core data sheet (CCDS). The CCDS includes the minimum safety relevant information that needs to be present on the product labels and any local labelling information for different geographies are derived from this.2

If and when the new ruling takes effect, generics companies will need to ensure they strengthen their pharmacovigilance operations and enforce rigorous safety monitoring

Every local labelling document (LL) devised from the CCDS could be different, depending on the geographic regions and on the product formulations. Complexity increases when these local labelling documents are in a different language with differing content. These local adaptations also need to be updated whenever there is a change in the CCDS due to availability of new safety, efficacy or product quality information and changes in regulatory landscape.

Changing regulatory requirements and the numerous hand-offs make the process more complex. The existing process of developing a product label is human resource-intensive and, therefore, requires extensive reviews and proofreading to ensure that the printed label is error-free. All of these factors add significantly to cost and time, not to mention being fraught with the possibility of introducing manual errors.


Today, the US FDA specifically requires a generic product to have the same label as the RLD. Therefore, even if the drug manufacturer is aware of any safety concern, the label of the generic product cannot be updated unless the RLD label is updated. This supports the business model of the generic drug companies, as they do not need to engage themselves in rigorous safety tracking like an innovator pharmaceutical company. It also largely grants the generic manufacturers immunity from being held accountable for not communicating key safety information to the consumer, or ‘failure-to-warn’.

Under the proposed rule, generic manufacturers will need to monitor safety events actively, and update the labels on receipt of new safety-specific information, by filing a CBE-0. This rule may then make the generic manufacturers accountable in ‘failure-to-warn’ cases and therefore, encourage the generic manufacturers to track the safety of their product more rigorously. Given the implications of this proposed rule, it has met with strong reactions from the industry, with more than 23,700 comments.

By employing a managed service model, potential clients can reap the benefits of end-to-end labelling workflow

One of the concerns has been that the ‘identical nature’ of the generic drug to the reference drug has been the reason for physicians to use the generic drugs with confidence. Also, the proposed rule would increase healthcare costs for consumers and government agencies due to the additional resources, processes and tools generic manufacturers will have to implement for enhanced safety tracking.

As the release date nears, the FDA itself will need to overcome issues that arise owing to the conflict between the proposed rule and the concept of generics as described in the Hatch Waxman Act.3 From a patient’s perspective, the new regulation is a step in the right direction in terms of equipping them with most updated safety information, but it may increase the cost of generic drugs. For the generic manufacturers, this rule has significant implications as they will be required to implement a safety tracking solution and processes for safety label updates.

If and when the new ruling takes effect, generics companies will need to ensure they strengthen their pharmacovigilance operations and enforce rigorous safety monitoring. Quality, efficiency and compliance must be underscored in an organisation’s labelling operations strategy, yet often these three elements are not in sync. Quality and compliance are mandatory, yet the resources, processes and costs required to meet these demands are a significant burden.

A product label from an innovator pharmaceutical company, prior to commercialisation, is drafted, then reviewed and approved by regulatory agencies, based on regulations and guidelines. Label maintenance, including safety updates, is an essential part of the innovator’s marketed products since they provide comprehensive information about the drug. They also represent a significant percentage of the manufacturing cost and commercialisation risk.

By contrast, a generic product label is based on the innovator label having already been approved by the regulatory authority. While a generic company’s portfolio may include 300 products, the RLD label could be sourced from 20–30 different innovator companies, compounding the complexities in referencing and tracking RLD updates. Labels are an integral part of the marketed product. They also represent a significant percentage of the manufacturing cost and commercialisation risk.

Labelling as a managed service

Labelling as a managed service is an externally managed, fully integrated platform of services, processes and technology enablers that covers the entire labelling continuum. The service includes expert labelling resources that execute global labelling activities on behalf of a sponsor or generics company. Oversight of the labelling workflow via key performance indicators (KPIs) and quality metrics can ensure an organisation is compliant with local and global regulations and efficient.

By employing a managed service model, potential clients can reap the benefits of end-to-end labelling workflow. Today, product labelling comprises disparate processes at different locations, based on country-specific preferences. A streamlined workflow management process, along with a document management system that allows for version control, and standardised label and artwork content, makes the task easier and more accurate, since it synchronises content and versions across geographies.

Organisations can ensure scale, performance, quality and compliance for labelling activities through a managed service by partnering with specialised service providers with global reach so that local regulations are also met. In summary, for generic manufacturers this proposed rule is a compelling reason for implementing processes for safety label updates and improved safety tracking, as they become increasingly accountable for ‘failure-to-warn’ cases.

From a patient’s perspective, this is a positive step in terms of equipping consumers with most up-to-date safety information. However, increased safety tracking may lead to increased cost to consumers. As the FDA makes it clear the rule will be rolled out later this year, it is expected that current hurdles will be solved, despite the controversy it has caused.





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